Chronic secondhand smoke exposure (SHSe) in children compromises pulmonary function and contributes to respiratory illness, wheeze, cough, asthma, middle ear disease, and sudden infant death syndrome. Preterm, low birth weight infants admitted to a Neonatal Intensive Care Unit (NICU) are especially vulnerable to the effects of SHSe, with many exhibiting significant respiratory or chronic lung conditions prior to discharge. Because smoking remains concentrated in less educated and impoverished communities, NICU families with household smokers are at significant risk for tobacco-related health disparities--a substantial burden to families with limited resources and the communities in which they reside. The primary aim of this investigation is to evaluate the efficacy of a hospital initiated, behavioral intervention to reduce household SHSe, compared to conventional care practices, in low-income, multi-ethnic parents of NICU infants at particularly high social and medical risk for adverse effects of SHSe. A randomized, controlled, parallel group design will be used to test whether a SHSe program initiated in the hospital and completed in the home using motivational interviewing plus motivational incentives (MI+) is more effective than Conventional Care (CC) with NICU parents. The effects of MI+ versus CC on household smoking and infant smoke exposure are expected to be mediated via motivation to change and treatment participation. A total of 396 families with an infant at high respiratory risk in the NICU who report a household smoker will be randomized. The MI+ intervention will consist of 4 one-hour counseling sessions (2 in the hospital; 2 in the home post-discharge) and incentives for both session attendance and establishing a home smoking ban. CC will involve written materials that include information about the effects of smoking and cessation tips discussed in meetings with a Family Life Coordinator. Counseling and interviews will be conducted in Spanish and English. Primary efficacy variables will include objective and valid measures of SHSe (infant cotinine, household air nicotine monitors, Timeline Followback for SHSe). Outcomes will be assessed at 1 and 6 months post-intervention using generalized linear mixed models, poisson and logistic regression. This will be the first study of an innovative combination of motivational strategies targeting SHSe within the context of a NICU to improve the health of vulnerable infants and their families, potentially saving millions in healthcare dollars. This trial may also demonstrate a practical means of accessing young, minority and economically disadvantaged families for preventive services, who are unlikely to present to traditional clinics for such care. Highly experienced behavioral and clinical investigators, pilot data suggesting intervention feasibility and promise, a large and accessible population, and an extraordinary infrastructure ensure study success. PUBLIC HEALTH RELEVANCE: Children chronically exposed to secondhand smoke (SHS) have diminished pulmonary function, and are more likely to suffer from respiratory infections, asthma, middle ear disease, poor growth, neurocognitive deficits, and sudden infant death syndrome. Low birth weight infants and infants at high respiratory risk admitted to a neonatal intensive care unit (NICU) are especially vulnerable to the effects of SHS, particularly given the poverty that exists among many NICU families who report a household smoker. Effective interventions to eliminate secondhand smoke exposure (SHSe) initiated in the NICU setting may reduce infant morbidity, mortality, and associated costs, and may reduce tobacco-related disparities in health.